Potential Participation of CTRP6, a Complement Regulator, in the Pathology of Age Related Macular Degeneration

Overview

Journal Jpn J Ophthalmol

Specialty Ophthalmology

Date 2022 Apr 9

PMID 35397057

Authors

Katsuhiko Shinomiya

Atsushi Mukai

Eiko Ito

Kazuhito Yoneda

Morio Ueno

Chie Sotozono

Shigeru Kinoshita

Junji Hamuro

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the localized expression of C1q/tumor necrosis factor related protein (CTRP) 6 in human age-related macular degeneration (AMD) retinal tissues.

Experimental Study Design: 4 AMD and 3 non-AMD whole eyes of Caucasian donors were used. Eyecups were excised at Eye Bank CorneaGen, Inc.

Methods: To elucidate the effects of CTRP6, C3b was measured by an enzyme-linked immunosorbent-like assay. CFB versus CTRP6 competitive binding assay was applied to clarify the inhibition by CTRP6 of C3bBb complex formation. The cornea, iris, lens, and vitreous were removed and the eyes were cut into a posterior eye-cup including the retina, choroid, and sclera. Six-µm-thick serial sections of frozen samples underwent hematoxylin-eosin (HE) staining and indirect immunohistochemical staining using primary antibodies, anti-CTRP6, -CTRP5, -CTRP10, -Complement factor H (CFH) and -Clusterin (CLU). Results The two in vitro studies confirmed that CTRP6 has an inhibitory effect on alternative pathways of complement (APC) function and that the molecular target of CTRP6 is the inhibition of the formation of C3bBb. Localized expression for CTRP6 and CFH was found in the drusen of the AMD eyes, both associated with APC inhibition, CLU associated with membrane-attack complex (MAC) inhibition, and CTRP5 associated with retinal degeneration.

Conclusion: The localized expression of CTRP6 in the drusen of AMD eyes may open a new insight into the possible involvement of APC regulatory factors in the pathogenesis of AMD, together with the known CFH so far analyzed solely as an APC inhibitor.

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PMID: 37705042 PMC: 10500765. DOI: 10.1186/s41927-023-00356-5.

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